Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial

Abstract

Introduction: Post-operative outcomes may be improved by the use of flow related end-points for intra-venous fluid and/or low dose inotropic therapy. The mechanisms underlying this benefit remain uncertain. The objective of this study was to assess the effects of stroke volume guided intra-venous fluid and low dose dopexamine on tissue microvascular flow and oxygenation and inflammatory markers in patients undergoing major gastrointestinal surgery.

Methods: Randomised, controlled, single blind study of patients admitted to a university hospital critical care unit following major gastrointestinal surgery. For eight hours after surgery, intra-venous fluid therapy was guided by measurements of central venous pressure (CVP group), or stroke volume (SV group). In a third group stroke volume guided fluid therapy was combined with dopexamine (0.5 mcg/kg/min) (SV & DPX group).

Results: 135 patients were recruited (n = 45 per group). In the SV & DPX group, increased global oxygen delivery was associated with improved sublingual (P < 0.05) and cutaneous microvascular flow (P < 0.005) (sublingual microscopy and laser Doppler flowmetry). Microvascular flow remained constant in the SV group but deteriorated in the CVP group (P < 0.05). Cutaneous tissue oxygen partial pressure (PtO2) (Clark electrode) improved only in the SV & DPX group (P < 0.001). There were no differences in serum inflammatory markers. There were no differences in overall complication rates between the groups although acute kidney injury was more frequent in the CVP group (CVP group ten patients (22%); pooled SV and SV & DPX groups seven patients (8%); P = 0.03) (post hoc analysis).

Conclusions: Stroke volume guided fluid and low dose inotropic therapy was associated with improved global oxygen delivery, microvascular flow and tissue oxygenation but no differences in the inflammatory response to surgery. These observations may explain improved clinical outcomes associated with this treatment in previous trials.

Trial registration number: ISRCTN 94850719.

Figure 1

CONSORT diagram; flow of patients through trial. *One patient randomised to the SV & DPX group developed myocardial ischaemia during surgery (before the trial intervention commenced) and, in accordance with the protocol, did not receive dopexamine. CVP, central venous pressure; DPX, dopexamine; SV, stroke volume.

Figure 2

Changes in (a) oxygen delivery index and (b) central venous oxygen saturation following surgery in the three treatment groups. *Significant difference between groups over time for oxygen delivery index (DO₂I) and central venous oxygen saturation (ScvO₂; P < 0.0001; two-way repeated measures analysis of variance). Significant increase in DO₂I over time: SV group P = 0.003; SV & DPX group P < 0.0001. Significant increase in ScvO₂ over time: SV & DPX group P < 0.0001; no change in the SV group (P = 0.22) or CVP group (P = 0.98). †At hour eight, there was a significant difference in DO₂I between the CVP and SV & DPX groups (P < 0.001) but no difference between the SV and CVP groups (P > 0.05). At hour eight, there was a significant difference in ScvO₂ between the CVP and SV & DPX groups (P < 0.05) but no difference between the SV and CVP groups (P > 0.05). CVP, central venous pressure; DPX, dopexamine; SV, stroke volume.

Figure 3

Changes in (a) sublingual perfused vessel density and (b) peak-baseline cutaneous red cell flux following three minutes of vascular occlusion from hour 0 following surgery in the three treatment groups. *Significant difference between groups over time for sublingual vessel density (P < 0.05) and cutaneous hyperaemic response (P < 0.01) (two-way repeated measures analysis of variance). Significant increase in perfused sublingual vessel density over time in the SV & DPX group (P = 0.046), no change in the SV group (P = 0.58) and a decrease in the CVP group (P = 0.005). Significant increase in cutaneous hyperaemic response over time in the SV & DPX group (P = 0.003), no change in the SV group (P = 0.58) and a decrease in the CVP group (P = 0.03). †At hour eight, there was a significant difference in perfused sublingual vessel density between the SV & DPX and CVP groups (P < 0.05) but not between the SV and CVP groups (P > 0.05). At hour eight, there was a significant difference in cutaneous hyperaemic response between the SV & DPX and CVP groups (P < 0.001) but not between the SV and CVP groups (P > 0.05). CVP, central venous pressure; DPX, dopexamine; SV, stroke volume.

Figure 4

Changes in tissue oxygenation following surgery in the three treatment groups. *Significant difference between groups over time (P = 0.0005; two-way repeated measures analysis of variance). Significant increase in tissue oxygenation (PtO₂) over time in the SV & DPX group (P = 0.0003), no change in the SV (P = 0.14) or CVP groups (P = 0.20). †At hour eight, there was a significant difference in PtO₂ between the SV & DPX and CVP groups (P < 0.005) but not between the SV and CVP groups (P > 0.05). CVP, central venous pressure; DPX, dopexamine; SV, stroke volume.

Figure 5

Changes in (a) serum IL-1β, (b) IL-6, (c) IL-8, (d) TNFα and (e) soluble inter-cellular adhesion molecule 1 between the three treatment groups. Data presented as mean (standard error). There were no significant differences between the groups. CVP, central venous pressure; DPX, dopexamine; ICAM-1, inter-cellular adhesion molecule 1; SV, stroke volume.